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The Effects of Intravenous Clomipramine on Neurohormones in Normal Subjects^*

Department of Psychiatry, University of North Carolina School of Medicine (R.N.G., R.H.) Chapel Hill, North Carolina 27599
The Clinical Pharmacology Section, Laboratory of Clinical Science, National Institute of Mental Health (J.H., S.R., W.Z.P.), and the Laboratory of Clinical Science, National Institute of Alcoholism and Alcohol Abuse (E.L.), National Institutes of Health Bethesda, Maryland 20892

Address requests for reprints to: Dr. Robert N. Golden, Department of Psychiatry, Campus Box 7160, Medical School Wing B, University of North Carolina, Chapel Hill, North Carolina 27599.

The neuroendocrine effects of iv administration of clomipramine (CMI), a serotonin reuptake inhibitor, were studied in normal subjects. Under double blind, placebo-controlled conditions, single 10- and 20-mg doses of CMI were administered. Ten milligrams of CMI led to significant increases in plasma PRL and cortisol concentrations; plasma ACTH increased slightly but not significantly. In contrast, plasma GH, melatonin, and norepinephrine concentrations did not increase. Plasma PRL, ACTH, and cortisol levels increased significantly after 20 mg CMI; again, there were no significant changes in plasma GH, melatonin, or norepinephrine concentrations. All subjects tolerated the 10-mg dose well, but the 20-mg dose caused nausea in three of six subjects. Desmethlyclomipramine, a me-tabolite that inhibits reuptake of norepinephrine, was not detectable in plasma after either CMI dose. These results support the hypothesis that serotonin is involved in the regulation of PRL, cortisol, and ACTH in humans.

^* This work was supported in part by NIMH Grants MH-42145 and MH-33127 and a research grant from the Foundation of Hope for Research and Treatment of Mental Illness.

Received March 29, 1988.

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